This might help

The content of this website should not be interpreted as medical advice. This might help is a collection of information, studies, and personal experience relating to supplements, medication and other treatments for a variety of chronic health conditions. Created out of necessity. Shared to help others.

Doxycycline / Doxycyclin

All information provided without any guarantee of accuracy. This does not constitute medical advice. Please consult your doctor fully before taking any medicine. You will need regular kidney/liver function tests, even when on a low dose – just as with many medications.


Doxycycline is generally known as a tetracycline-type antibiotic. It is also an MMP-inhibitor with several non-antibiotic uses – many of which can still be accessed at subantimicrobial doses (as in, 20 mg twice daily – shown to not affect gut or vaginal flora, as opposed to the more standard dose of 100 mg twice daily when used as an antibiotic.

It is a mast cell inhibitor, meaning it helps treat inflammation and allergies. This makes it useful in related conditions, such as mastocytosis, or, off-label, mast cell activation disorder.

Doxycycline also enhances wound healing and is used on-label in subantimicrobial doses to treat inflammatory conditions such as rheumatoid arthritis and periodontitis, and sometimes acne.

Its potential antiviral properties against SARS coronavirus have been studied. MMP inhibition comes up again, but that debate and the unhelpful politicisation of illness and medicine is far beyond the scope of this page. Do your own googling if interested!

Known effects

See above. The big thing with doxycycline is to remember that it’s more known for its antibiotic properties, but its MMP inhibition properties are especially interesting for people with MCAS, Ehlers-Danlos Syndrome, wound healing issues, and inflammation.

Studies show that the sub-antimicrobial dose of 20 mg twice a day does not affect gut or vaginal flora. It is also shown to be sufficient to achieve the MMP inhibition benefits in multiple studies. This makes long-term use of low-dose doxycycline far more viable, though it must still be carefully monitored. Anecdotally, is more commonly used in the treatment of MCAS in the United States.

Doxycycline is known to deactivate an enzyme produced by EDS patients in a petri-dish study. The result was that collagen would grow like normal collagen while doxycycline is present. The limitations of the study are self-evident, but the implications are interesting.

MMP-9 inhibition by taking low-dose doxycycline was shown to support the healing of venous leg ulcers – notoriously hard to heal. This may have implications for other issues with slow healing.

Rose takes this like this

I discovered the effectiveness of doxycycline by chance, when I took it first at 100 mg twice a day for a week to treat a stubborn urinary tract infection, then found most of my other symptoms (of MCAS, POTS, EDS, ME/CFS, long covid and NDPH) greatly reduced and even subsided in the case of NDPH, new daily persistent headache. I continued this off-label for a total of 8 weeks, in which my face transformed back to the pre-covid shape and I saw massive improvements.

That dose isn’t safe for long-term use. So I went off it. But then all my symptoms returned. The NDPH and ME/CFS came back especially fast, and within a few months, lymph buildup was significant again.

Recently, I found an understanding neurologist who agreed that my migraines are actually NDPH, and that my experience correlates with the fact doxycycline (alongside montelukast) has been found to treat NDPH in one case study. He agreed we could give it another go.

While he was willing to prescribe at the full dose for a limited period to see how it goes, I read more studies in the meantime that suggested the lower subantimicrobial dose is sufficient. Not wanting to worry my doctors any more than necessary, I decided to give the subantimicrobial dose a try – also since this would be an option for long-term, off-label treatment of my debilitating NDPH, while also helping with other symptoms.

20 mg pills are not available in Germany, so I have been prescribed 50 mg pills that can be split in half, to give me 25 mg, to be taken twice daily. This should still be a sub-antimicrobial dose. The antibiotic dose would start at 100 mg and up – although some studies suggest gut flora changes have been observed at doses of 50 mg and up. Thus, lower is better.

I’ve only just started on this lower dose, but initial signs are good. I’ve experienced the same complications of healing as last time, with a sleepy phase, and a hyperactive phase as my body couldn’t figure out how to deal with the changes in pain and energy levels. It almost instantly reduced the pain in my hip that had stopped me from leaving my street for the past three months. The physio can perceive some changes, too. It’s early days, but my first impressions are that it works, though may be a little slower than at the higher dose. The sleep problems have since been fixed beautifully with Clonidine 0.75 mcg at night.

Anecdotally, full-dose doxycycline appears to have also helped a friend with EDS and vaccine-linked long covid. She’s now trying to get low-dose doxycycline prescribed for MCAS. A male friend of a friend with EDS and MCAS got it prescribed on a low dose, but didn’t tolerate it.

Given the strong connection between Ehlers-Danlos and tauopathies (Alzheimer’s, Parkinson’s and co.), it’s hard to imagine why patients with EDS and neurological (mental) symptoms should not be put on low-dose doxycycline as a preventative measure against tauopathies while also calming mast cells. One of the studies on the right shares this general suggestion, not in relation to EDS.

Who might prescribe this?

I was prescribed this for New Daily Persistent Headache by a neurologist. A friend of a friend was prescribed this for MCAS by an allergist. This is more commonly prescribed in the US for MCAS, but MCAS specialists are thin on the ground in Europe.


Tetracyclines in general work in similar ways. Research that applies to minocycline, doxycycline or tetracycline itself can be anticipated to somewhat apply to the other types, with some differences. Allergic reactions tend to apply to all in the group, as far as I know.

Merely as a pointer, the macrolide group of antibiotics seem to have similar effects at a mitochondrial level and have also been used at low doses for their immunomodulatory effects. Anecdotally, I can report that topical erythromycin in an acne gel, alongside benzoyl peroxide, had the same strange positive effect as oral doxycycline in making my skin much stronger and smoother – more like the skin of someone without Ehlers Danlos. Initial reading suggests erythromycin also has an MMP-9 inhibition effect and is sometimes used for anti-inflammatory and anti-fungal benefits, making it likely macrolides could achieve some of the same things as tetracyclines.

I get on well with doxycycline so haven’t read more into it, so you can just take that as a pointer for your own research. Please let me know what you find!


Safety of long-term use in subANTImicrobial doses

Long-term use of subantimicrobial dose doxycycline does not lead to changes in antimicrobial susceptibility (2000)
In short, no risk of antibiotic resistance from long-term subantimicrobial use of doxycycline.

Subantimicrobial Dose Doxycycline Effects on Osteopenic Bone Loss: Microbiologic Results (2007)
Safety of long-term low-dose doxycycline confirmed in osteopenic women with periodontitis – no change in flora, no antibiotic resistance.

MCAS and Anti-inflammatory effects, incl. lung function

Anti-Inflammatory Properties of Low and High Doxycycline Doses: An In Vitro Study (2015)
This in vitro study validates the effectiveness of low- and high-dose doxycycline in the treatment of inflammatory conditions, though low-dose doxycycline appears to be more effective (as well as safer).

Minocycline: far beyond an antibiotic (2013)
This extensive review covers the various interesting positive effects of the closely related fellow tetracycline, minocycline, on neurodegenerative diseases and inflammatory issues.

The Inhibitory Effects of Tetracycline on Mastocytosis (2019)
This study details how tetracyclines (including doxycycline) can treat mastocytosis. Mastocytosis and mast cell activation syndrome are not the same thing, but many (most? all?) treatments for mastocytosis will also work well on MCAS patients.

Doxycycline reduces airway inflammation and hyperresponsiveness in a murine model of toluene diisocyanate–induced asthma (2004)
Not all the study is available, but this seems to suggest doxycycline can reduce airway inflammation and hyperresponsiveness in TDI-induced asthma in rodents.

Doxycycline exerts multiple anti-allergy effects to attenuate murine allergic conjunctivitis and systemic anaphylaxis (2014)
Not all the study is available, but this talks about how doxycycline calms mast cells in mice while explaining the method of action. Especially interesting to MCAS patients.

Doxycycline as an anti-inflammatory agent: updates in dermatology (2017)
I don’t have full access, but this summarises doxycycline’s anti-inflammatory properties.

Impact of long-term doxycycline on lung function & exacerbations: A real-world open, prospective pilot observation on chronic obstructive pulmonary disease (2021)
Long-term use of high-dose doxycycline (100 mg, seemingly once a day) was stated to seem to “improve lung function, health status and exacerbations in COPD”, while also being well tolerated. They focused on MMP-2, MMP-9 and CRP levels. The first two show what they were aiming for, while the CRP (C-Reactive Protein) is a good general measure of inflammation. The study of MMP-2 and MMP-9 levels, however, indicated that they most likely didn’t need to use the antibiotic dose and would have seen similar results on a safer subantimicrobial dose. The study showed impressive results regardless – my niggle about using an unnecessarily high dose doesn’t change that.

Benefits in Ehlers-Danlos and related conditions

Matrix Metalloproteinases Inhibition by Doxycycline Rescues Extracellular Matrix Organization and Partly Reverts Myofibroblast Differentiation in Hypermobile Ehlers-Danlos Syndrome Dermal Fibroblasts: A Potential Therapeutic Target (2021)
This is the big one, really. In short, doxycycline makes Ehlers-Danlos collagen look the same as the collagen of patients without Ehlers-Danlos under the microscope – in an extensive in-vitro study. This is linked to MMP inhibition. The summary here is worth reading:

Tetracyclines Inhibit Connective Tissue Breakdown by Multiple Non-Antimicrobial Mechanisms (2016)
This study explains doxycycline’s protective effects on connective tissue especially through its MMP inhibition effects, including its effect on collagenase. It goes without saying that this is going to directly relate to its effects in connective tissue disorders such as Ehlers-Danlos Syndromes or Marfan Syndrome.

Vascular benefits in Marfan and Ehlers-Danlos, incl. prevention of aneurysms

Long-Term Doxycycline Is More Effective Than Atenolol to Prevent Thoracic Aortic Aneurysm in Marfan Syndrome Through the Inhibition of Matrix Metalloproteinase-2 and -9 (2008)
This study shows long-term subantimicrobial (low-dose) doxycycline works better than a beta-blocker in preventing one of the worst complications of Marfan Syndrome.

Doxycycline Delays Aneurysm Rupture in a Mouse Model of Marfan Syndrome (2008)
Doxycycline was found to significantly delays aneurysm rupture in Marfan-like mice by inhibiting MMP-2 and MMP-9, consequently preventing degradation of the elastic matrix. MMPs are assumed to play a role in the progression of thoracic aneurysm in Marfan. Doxycycline is therefore promising.

Characterization of doxycycline-mediated inhibition of Marfan syndrome-associated aortic dilation by multiphoton microscopy (2020)
Marfan Syndrome is extremely closely related to Ehlers-Danlos Syndromes. This study interestingly reports the exact same improvements that I and a friend with EDS observed when on doxycycline – namely, that our skin improved in a really obvious way. It suggests this is reflective of hidden aortic improvements, which would explain our dramatic loss of lymph and improvement of POTS and fatigue symptoms. The conclusion is worth reading in full, but to tempt you, I’ll include this excerpt:
“In addition, we found that skin dermal thinning observed in MFS [Marfan] is attenuated by doxycycline treatment, and that decreased thickness of the dermal layer is positively associated with increased levels of aortic fiber disorganization and medial thickening. Our findings open a new direction for testing the hypothesis that the degree of skin dermal thickness could possibly be considered as a maker for changes in aortic wall structure and integrity. Further clinical studies that allow for the examination of structural changes in the dermis and epidermis and establishing a potential correlation between dermal skin and aortic events in MFS patients can provide information about the diagnostic or prognostic values of such assessments in these patients.”

Doxycycline Ameliorates the Susceptibility to Aortic Lesions in a Mouse Model for the Vascular Type of Ehlers-Danlos Syndrome (2011)
This one has too serious implications for me to even risk summarising it. They do, however, talk about MMP-9 specifically. Worth reading and discussing with your doctor in connection with the one above if you have vascular EDS or a related condition, or another type of EDS but with vascular involvement.

Wound healing in connection with MMP-9

Doxycycline speeds up healing of chronic venous ulcers (2013)
Very interesting study on wound healing, showing how low-dose doxycycline (they used 20 mg twice a day) sped up healing of notoriously tricky chronic venous ulcers. Lower MMP-9 levels come up again. This may have implications for other wounds that are slow to heal. It’s great that they proved effectiveness at a subantimicrobial dose.


Low dose doxycycline decreases systemic inflammation and improves glycemic control, lipid profiles, and islet morphology and function in db/db mice (2017)
“Glucose and insulin tolerances were improved, accompanying with reduced fasting blood glucose, insulin, HOMA-IR and advanced glycation end products.” and ultimately “The results support further study of possible long-term usage of sub-antimicrobial doxycycline in diabetic patients.”
Yes, really. A dirt-cheap drug at a safe subantimicrobial dose can treat diabetes. I don’t know what to say about the lack of further research and approval.

Effect of Doxycycline vs Placebo on Retinal Function and Diabetic Retinopathy Progression in Patients With Severe Nonproliferative or Non–High-Risk Proliferative Diabetic RetinopathyA Randomized Clinical Trial (2014)
The study suggests a link between a low-dose oral anti-inflammatory agent – doxycycline here – and subclinical improvement in inner retinal function. They believe this is down to the anti-inflammatory effect.

Doxycycline in Extremely Low Dose Improves Glycemic Control and Islet Morphology in Mice Fed a High-Fat Diet (2021)
“Our results suggest that doxycycline, even at an extremely low dose, could improve glycemic control and islet morphology via its anti-inflammatory activities.”

Doxycycline Induced Hypoglycemia in an Adult without Diabetes (2018)
Being effective as it is against diabetes, it seems doxycycline also carries the risk of inducing hypoglycemia in some non-diabetic patients. Since it is not specified here, this is almost certainly talking about the full antibiotic dose of 100 mg twice a day, or similar.

Uncommon side effect of a common drug: doxycycline induced hypoglycaemia (2022)
Similar to the above, same issue in another older male. They suggest a couple of explanations, including insulin resistance.

NDPH migraines

New daily persistent headache: an update (2014)
As above. This shows how doxycycline combined with montelukast (a mast cell inhibitor) helped in the treatment of NDPH. However, my own theory is they probably didn’t need to dose the doxycycline so high to get the MMP-9 inhibition effects at the root of the successful treatment.

New daily persistent headache: a systematic review on an enigmatic disorder (2019)
NDPH is a post-infectious migraine with a defined onset date. This makes its treatment options interesting to long covid patients with these symptoms who fit a similar pattern. The doxycycline/tetracycline findings by Rozen are explained quite well here.

Tauopathies, Multiple Sclerosis, Parkinson’s, Alzheimer’s and mental health

Doxycycline at subantimicrobial dose combined with escitalopram reverses depressive-like behavior and neuroinflammatory hippocampal alterations in the lipopolysaccharide model of depression (2021)
This study seems to suggest that low-dose doxycycline, even used alone, could revert inflammatory changes in the brain and protect against depression.

Doxycycline restrains glia and confers neuroprotection in a 6-OHDA Parkinson model (2013)
Word for word, this study says: “The neuroprotective effect of doxycycline may be useful in preventing or slowing the progression of Parkinson’s disease and other neurodegenerative diseases linked to glia function.”

Doxycycline Interferes With Tau Aggregation and Reduces Its Neuronal Toxicity (2021)
The pathological aggregation of tau or neurofibrillary tangles are known as tauopathies, part of many neurodegenerative diseases, most notably Alzheimer’s and Parkinson’s. This fascinating study ultimately proposes low-dose doxycycline as a preventative treatment for tauopathies such as Alzheimer’s and Parkinson’s. The strong connection between Ehlers-Danlos and tauopathies underlines the urgency of the question of whether EDS and other connective tissue disorder patients should be given low-dose doxycycline as a preventative measure against tauopathies while also calming mast cells and improving vascular/endothelial function.

Tau seeding in cases of multiple sclerosis (2022)
In short, Multiple Sclerosis may be a secondary tauopathy.

Non-fluent progressive aphasia, depression, and OCD in a woman with progressive supranuclear palsy: neuroanatomical and neuropathological correlations (2006)
It’s just one case study, but it’s especially relevant given the comorbidity of neurodivergence and mental illness and Ehlers-Danlos Syndromes. Quote from the paper: “This case highlights the fact that frontotemporal lobar degeneration/progressive supranuclear palsy (FTLD/PSP) and other “tauopathies” represent a complex group of neurodegenerative disorders that may masquerade for many years as refractory psychiatric disorders.”
Ergo, the doxycycline – tau aggregation function is especially relevant to people at risk of tauopathies, which may well include EDS patients.

Ehlers-Danlos syndrome and multiple sclerosis: a possible association (2008)
EDS is found about 10-11x more in the MS sample compared to the general population, suggesting a related causal link.

Trial of Minocycline in a Clinically Isolated Syndrome of Multiple Sclerosis (2017)
Some suggestion minocycline may reduce onset of full MS at six months, but the results weren’t sustained at two years – further research required.

Myalgic Encephalomyelitis (ME) / Chronic Fatigue Syndrome

Oral Minocycline Therapy Improves Symptoms of Myalgic Encephalomyelitis, Especially in the Initial Disease Stage (2021)
A study on ME patients using a full-dose of the closely related tetracycline, minocycline, showed an improvement in symptoms in those able to participate. Note that orthostatic intolerance, of which postural orthostatic tachycardia syndrome is one form, was observed in the patients. Improvements were observed, especially in patients within the first three years of diagnosis. However, there was a high drop-out rate due to side effects. My own thinking is that a lower dose may be equally beneficial without such widespread side effects, but that they may have gone down the antibiotic treatment route due to other studies showing effective treatment of ME or ME-like symptoms following viral infections, such as Q fever, or the widely recognised treatments for Lyme Disease. Other findings suggest an antibiotic dose may not be necessary, depending on the mechanism of action.

Potential role of licofelone, minocycline and their combination against chronic fatigue stress induced behavioral, biochemical and mitochondrial alterations in mice (2012)
The related antibiotic, minocycline, helped reduce chronic fatigue stress in mice – in combination with licofelone.

A chronic fatigue syndrome model demonstrates mechanical allodynia and muscular hyperalgesia via spinal microglial activation (2014)
Minocycline significantly reduced chronic stress-induced mechanical sensitivity to pain and neuropathic pain in rats. Activated microglia were thus suspected to be involved in the development of abnormal pain in affected animals. Minocycline was not the focus here – it was used to reduce pain and prove that pain in CFS/ME and fibromyalgia patients may be partly caused by something relating to microglial activation. The natural implication, seemingly taken as read by the researchers, is that minocycline can reduce pain-related issues in ME/CFS.

Could Minocycline Be a “Magic Bullet” for the Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome? (2021)
This letter (with references) explains similar thinking to elsewhere on this page, right down to the low-dose use of antibiotics and the use of the macrolide antibiotic erythromycin in a long-term, anti-inflammatory application. His reasoning is that ME/CFS patients experience neuroinflammation (as shown in other studies), so using a low-dose antibiotic such as minocycline could reduce symptoms.

Neuropathic pain

Mast cell activation disease: An underappreciated cause of neurologic and psychiatric symptoms and diseases (2015)
Here tetracyclines are mentioned again as a potential treatment for neuropathic pain. The rest of the paper is interesting in relation to the aforementioned mental health and neurological connections.

Minocycline prevents the development of neuropathic pain, but not acute pain: Possible anti-inflammatory and antioxidant mechanisms (2008)
Similar to the above. Again, minocycline is very closely related to doxycycline.

Endometriosis and Pregnancy

Doxycycline reduces MMP-2 activity and inhibits invasion of 12Z epithelial endometriotic cells as well as MMP-2 and -9 activity in primary endometriotic stromal cells in vitro (2019)
Doxycycline’s MMP inhibition effects shown to be promising against infiltrative endometriosis (e.g. endometriosis that’s moved into other pelvic organs).

Doxycycline causes regression of endometriotic implants: a rat model (2009)
In this study, doxycycline caused a regression (improvement) of endometriosis implants in rats.

CERM: Can doxycycline prevent miscarriage in women with endometritis? (2018 to 2024)
This is an interesting study in progress. They aim to give women with a history of miscarriage identified to have endometriosis doxycycline for 14 days before trying to conceive. The dose is not revealed, though the duration might suggest a full antibiotic course.

Revisiting doxycycline in pregnancy and early childhood – time to rebuild its reputation? (2016)
Doxycycline has previously been advised against in pregnancy and early childhood. However, a systematic review reveals doxycycline does not share the issues found in its “parent”, tetracycline.

Emerging treatment of endometriosis (2015)
Doxycycline is included in the MMP section of this review of treatments for endometriosis.

Covid-19, long covid and how MMP inhibition may help

Targeting MMP-Regulation of Inflammation to Increase Metabolic Tolerance to COVID-19 Pathologies: A Hypothesis (2021)
This is merely a hypothesis, but may explain part of how doxycycline seems especially helpful in the treatment of long covid.


Mitonuclear protein imbalance as a conserved longevity mechanism (2013)
Here’s a wildcard – one that I don’t fully understand. It seems to suggest that doxycycline, including low-dose doxycycline, increase longevity in mice and worms. It has to do with MRP and proteins. As an aside, there’s a fundamental link between MRP issues and EDS. If a doctor fancies explaining the full implications of this to me in the comments, I’d be grateful!

Other links

News on minocycline research from the MS Society – on how minocycline may help in Multiple Sclerosis.

Andere Links auf Deutsch

Doxycyclin zur antibiotischen Parodontitisbehandlung

Note: This is a work in progress. There are a lot of studies about doxycycline, making it hard to select just a few to feature here. I hope I’ve included all you need, but if you think there’s an important one I missed, please comment below.


2 responses to “Doxycycline / Doxycyclin”

  1. Rain avatar

    Hello, I would really appreciate hearing more from you about if this continues to have helped your long covid. I’m a 49
    Year old woman suffering with long covid. I’m going to get a prescription and try the low dose pattern. Any extra info on side effects or tips is much appreciated.
    Warm regards,

  2. Sally Finnegan avatar
    Sally Finnegan

    Oh my goodness. Thank you for your work! I have hEDS and had to take a prophylactic dose of amoxicillin the other morning before a dental procedure. The dose was 1.5g. I should have felt poorly that day because I had two nights in a row with less than 7 hours sleep and it was rainy, meaning the barometric pressure was low that day. Instead I felt good. I noticed I could walk more easily and with much less pain. I then recalled another piece I read a couple of years ago about a woman with hEDS who also discovered that antibiotics virtually took her symptoms away. I thought she was in the US. So I did a search and came across your article. Thank you very much

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